Experimental Study Of MRI-Guided Microwave Ablation Combined With Clostridium Novyi-NT Spore In The Treatment Of VX2 Rabbit Liver Cancer

Part 1 Efficacy and Safety of MRI and CT Guided VX2 Hepatic Para-vascular Tumor Model in RabbitsObjective:To compare the efficacy and safety of 1.5T MRI and CT guided VX2 hepatic para-vascular tumor model in rabbits.Methods:Sixty New Zealand white rabbits were randomly and equally divided into MRI-guided group(n=30)and CT-guided group(n=30).Rabbit VX2 tumor fragments was implanted beside the rabbit hepatic great vessels under MRI and CT-guidance in the MRI and CT group respective,to evaluate the success rate of tumor model establishment,puncture needle pseudopacity/artifact and vascular development around the needle tip,operation time and safety.Result:In MRI-guided group,29 rabbits(29/30,96.7%)had successful establishment of liver tumor model,1 rabbit had needle metastasis.In CT-guided group,24 rabbits(24/30,80%)had successful establishment of liver tumor model while,2 rabbits had needle metastasis,3 rabbits had metastases in other parts of the liver,and 1 had unknown cause of death.The differences in success rate of tumor model establishment between the two groups was statistically significant(P<0.05).The fold number of artifacts at T1WI was 7.26±0.38 for the 20G coaxial puncture needle in the MRI-guided group and 2.51± 0.57 for the 20G coaxial puncture needle in the CT-guided group,and the difference was statistically significant(P<0.01),but 13 rabbits(13/30,43.3%)in the CT-guided group showed star-shaped hypodense artifacts would appear around the needle tip,which interfered with intrahepatic vascular display,and the difference was statistically significant(χ2=8.523,P<0.01).The operation time was longer in the MRI-guided group than in the CT-guided group(13.32±2.45 minutes in the MRI-guided group vs 8.42±1.46 minutes in the CT-guided group;P<0.01).A small amount of ascites occurred in 2 rabbits(2/30,6.67%)in the CT-guided group;no serious complications such as liver abscess,jaundice or diaphragmatic perforation were observed in either groups.Conclusion:Compared with CT,MRI-guided hepatic paravascular tumor implantation in rabbits might be a more effective modeling method.Although the needle tip pseudopacity of puncture needle is large and the operation takes a long time,the vascular development around the needle tip is clear and the incidence of complications is low.Part 2 Experimental Study of MRI-Guided Microwave Ablation Combined with Clostridium novyi-NT Spore in the Treatment of VX2 Rabbit Liver CancerObjective:To evaluate the efficacy of microwave ablation(MWA)combined with Clostridium novyi-NT(C.novyi-NT)spores in the treatment of rabbit VX2 liver cancer.Methods:C.novyi-NT spores were sporulated and purified for future use after at least 14 days of anaerobic culture.Forty-eight rabbit VX2 liver cancer models successfully established in the first part were randomly selected.They were randomly and equally divided into four groups:control group(group A,12n),MWA group(group B,12n),intratumoral injection of C.novyi-NT group(group C,12n),MWA combined with intratumoral injection of C.novyi-NT group(Group D,12n).MRI scans were performed on the 7th and 21 st day after treatment in each group of experimental rabbits to measure the tumor size,extent of necrosis,proportion of tumor volume reduction and the proportion of intratumoral necrosis.On 21st day,4 rabbits in each group were randomly selected and venous blood was collected.The rabbits were then sacrificed,dissected and sampled(3 tissue blocks were randomly taken from each tumor and necrosis area)for bacterial culture and bacteria in the blood,tumor,tumor ablation necrosis area and important organs.The survival time of the remaining 8 experimental rabbits in each group was observed.Result:Culture and purification of C.novyi-NT spores was successfully achieved.All treatments were completed as planned in all 48 experimental rabbits.There was no statistically significant difference in the proportion of tumor volume reduction between group B and D on post treatment day 7(P>0.05,Mann Whitney test).The proportion of tumor volume reduction in group D was significantly higher than that in groups A,B,and C on post treatment day 21(PAD<0.001,PBD<0.05,PCD<0.001,Mann Whitney test).On the 21st day post treatment,the proportion of tumor necrosis in group D was significantly higher than that in groups A,B,and C(PAD<0.001,PBD<0.05,PBC<0.05,PCD<0.001,Mann Whitney test).Bacterial culture found that a large number of bacteria were distributed in the tumor tissue and tumor ablation necrosis area,but no bacterial germination was observed in the heart,liver,spleen,lung,kidney tissues and blood.The mean survival time of groups A,B,C,and D was 30.38±4.69 days,56.13±4.31 days,46.43±5.50 days,and 73.38 ±9.35 days,respectively.Kaplan Meier survival curves showed that the survival rate of group D was significantly higher than that of the other three groups(P<0.001,Log Rank test).Conclusion:MWA combined with C.novyi-NT spores in the treatment of rabbit VX2 liver cancer can rapidly and effectively reduce the tumor size,expand the tumor necrosis area,and significantly prolong the survival time of experimental rabbits.